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Methionine Functionalized Biocompatible Block Copolymers for Targeted Plasmid DNA Delivery
Published on: August 6, 2019
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Total Methionine Restriction Treatment of Cancer
Robert M Hoffman1,2, Demetrius M Kokkinakis3, Eugene P Frenkel4
1AntiCancer, Inc., San Diego, CA, USA. all@anticancer.com.
Methods in Molecular Biology (Clifton, N.J.)
|February 7, 2019
Summary
Total methionine restriction (MR), achieved with a special diet and enzyme therapy, significantly enhances chemotherapy for brain tumors in mice. This approach slows tumor growth and potentiates standard treatments like BCNU and temozolomide.
Area of Science:
- Oncology
- Biochemistry
- Pharmacology
Background:
- Methionine (MET) is an essential amino acid crucial for cell proliferation.
- Cancer cells often exhibit higher dependence on methionine metabolism.
- Targeting methionine metabolism presents a potential therapeutic strategy for brain tumors.
Purpose of the Study:
- To investigate the efficacy of total methionine restriction (MR) in potentiating chemotherapy for human brain tumor xenografts in mice.
- To evaluate the combined effects of a methionine-free diet, recombinant L-methionine-α-deamino-γ-lyase (rMETase), and standard chemotherapeutic agents.
Main Methods:
- Human brain tumor xenografts (Daoy, SWB77, D-54) were established in nude mice.
- Methionine restriction was induced using a combination of an MR diet and rMETase, achieving plasma methionine levels below 5 μm.
- Homocysteine was administered to rescue normal cells.
- Chemotherapeutic agents, N,N'-bis(2-chloroethyl)-N-nitrosourea (BCNU) and temozolomide (TMZ), were administered post-MR regimen.
Main Results:
- Total MR effectively arrested the growth of Daoy, SWB77, and D-54 xenografts.
- MR alone inhibited tumor growth but did not prevent regrowth after treatment cessation.
- A single dose of BCNU following MR resulted in >80-day growth delay for Daoy and D-54, and a 20-day delay for SWB77.
- MR treatment regimens enhanced the efficacy of TMZ against the SWB77 xenograft.
Conclusions:
- Total methionine restriction is a potent strategy to enhance the efficacy of standard chemotherapy for brain tumors.
- Combining MR with agents like BCNU and TMZ shows significant promise in controlling brain tumor xenograft growth in preclinical models.
- Targeting methionine metabolism offers a viable approach to overcome therapeutic resistance in brain cancers.
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